ABSTRACT The Muscle-Bone Imaging Core (Core B) will support the research aims of all projects within this program project. The overall aim of the program project is to understand the mechanisms underlying crosstalk between muscle and bone that may contribute to the age related decline in muscle and bone mass and function. Another goal is to determine if muscle-bone crosstalk mediates some of the beneficial effects of exercise on the musculoskeletal system. This global question is addressed by each project from a different perspective, including: the effects of the muscle-derived factor, BAIBA, in old and young osteocytes (Project 1); the effects of osteocyte factors Wnt3a and PGE2/Wnt-?-catenin on muscle with aging (project 2); the role of extracellular vesicles in bone-muscle crosstalk with aging (Project 3); and estrogen receptor-mediated regulation of bone-muscle crosstalk with aging (Project 4). The Muscle-Bone Imaging Core will provide centralized imaging support and methodologies for all projects. This will include confocal and multiphoton 3D and live cell and intravital imaging of muscle and bone as well as histological preparation and staining of muscle tissues and mineralized tissues. It will also support quantitative histomorphometry and dynamic bone histomorphometry, immunohistochemistry, muscle fiber typing and 3D osteocyte confocal imaging as well as live imaging of mitochondrial dynamics and function. The core will standardize and integrate imaging techniques essential for all the projects in which muscle and bone phenotypes are being characterized as a function of age in transgenic mouse models with altered osteocyte or muscle function, as well as mice that have been subjected to exercise training. The Muscle-Bone Imaging Core is critical to the success and outcomes in all four projects. The technical expertise, instrumentation, quantitative analysis and standardized protocols of the Core will provide a centralized shared resource that will accelerate and enhance the research. Core B will coordinate its activities with the Animal Exercise and Analysis Core (Core C) to support the research aims of all the projects and to assist with characterizing the beneficial effects of exercise on the musculoskeletal system and how this is mediated by muscle-bone crosstalk. Successful completion of the research aims of these projects will provide new insight into why osteoporosis and sarcopenia occur together and may identify molecular mediators of common pathogenic mechanisms and of the beneficial effects of exercise, which may pave the way for development of new therapies. As muscle weakness contributes to falls that lead to fractures, new therapies addressing both aspects of this ?muscle-bone loss syndrome? will improve quality of life and reduce mortality in the aged population.